1. Field of the Invention
The present invention relates generally to the field of molecular biology, immunology and oncology. More particularly, it concerns diagnostic methods for predicting a response to an immunotherapy.
2. Description of Related Art
More than 70,000 new cases of bladder cancer are diagnosed yearly, with the majority presenting as superficial, i.e. non-muscle-invasive bladder cancer (NMIBC) (Jemal et al., 2010). Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed cases, and comprise a heterogeneous group whose individual prognoses are difficult to predict. Sixty percent to 70% of non-muscle invasive tumors recur and 10% to 40% progress to muscle-invasive disease (Heney et al., 1983). The standard treatment for NMIBC is transurethral resection followed by adjuvant intravesical therapy with BCG (Bacillus Calmette Guerin), the most effective intravesical treatment, for high-risk patients (Kamat and Lamm, 2001); however, a significant number of patients fail treatment (70% tumor recurrence) and require more aggressive intervention, such as radical cystectomy and/or chemotherapy. Currently, post-transurethral resection (TUR) surveillance is performed by cystoscopy and urine cytology at regular intervals. As such, clinicopathological variables remain the only prognostic predictors and these include tumor grade, tumor stage, tumor size, number of tumors, and location of the tumors. These variables rely on detection of actual tumor recurrence and are poor predictors of therapy failure making it hard to predict the effectiveness of therapy prior to recurrence of the tumor (Dalbagni et al., 1999; Highshaw et al., 2003). If patients do not respond to intravesical BCG, performing radical cystectomy within the first 24 months after diagnosis is believed to improve survival by at least 20% (Herr and Sogani, 2001). The ability to preemptively identify patients who are destined to recur will have tremendous impact since it would allow clinicians to provide patients with a tailored approach to their disease and provide individualized knowledge of whether their treatment is efficacious. Thus, early identification of patients in whom BCG will fail would allow those patients to receive earlier curative radical cystectomy and improve their chances of survival. New minimally invasive tests are clearly needed to increase the accuracy of prediction of recurrence, especially in patients treated with BCG.